Identification of ERAD-dependent Degrons for the Endoplasmic Reticulum Lumen

Overview

Journal Elife

Specialty Biology

Date 2024 Nov 12

PMID 39531282

Authors

Rachel Sharninghausen

Jiwon Hwang

Devon D Dennison

Ryan D Baldridge

Affiliations

Soon will be listed here.

Abstract

Degrons are minimal protein features that are sufficient to target proteins for degradation. In most cases, degrons allow recognition by components of the cytosolic ubiquitin proteasome system. Currently, all of the identified degrons only function within the cytosol. Using , we identified the first short linear sequences that function as degrons from the endoplasmic reticulum (ER) lumen. We show that when these degrons are transferred to proteins, they facilitate proteasomal degradation through the endoplasmic reticulum associated degradation (ERAD) system. These degrons enable degradation of both luminal and integral membrane ER proteins, expanding the types of proteins that can be targeted for degradation in budding yeast and mammalian tissue culture. This discovery provides a framework to target proteins for degradation from the previously unreachable ER lumen and builds toward therapeutic approaches that exploit the highly conserved ERAD system.

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